Functional Ontogeny of Pulmonary Vascular Dopamine Receptors in the Isolated Perfused Rabbit Lung

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Abstract

ABSTRACT

Using an in situ isolated salt-perfused rabbit lung preparation, we investigated the functional ontogeny of pulmonary vascular dopamine receptors. In rabbits from 1 to 23 d of age, we measured pulmonary vascular vasodilator) responses to the peripheral vascular dopamine receptor (DA1) agonist, fenoldopam, and sodium nitroprusside during prostaglandin F2α-induced pulmonary vasoconstriction. In separate experiments, the lungs were pretreated with the DA1 receptor blocker, SCH 23390, before prostaglandin F2α, fenoldopam, and sodium nitroprusside. Lungs from rabbits at one of 6 age groups (n = 6–8 per group) were ventilated and perfused. After a stabilization period, prostaglandin F2α was infused into the pulmonary inflow catheter in a concentration range to yield a sustained rise in mean pulmonary artery pressure (4.9 ± 0.2 mm Hg). Fenoldopam was injected into the pulmonary artery at doses of 0.01, 0.1, 1.0, and 10 μg/g after a recovery period, sodium nitroprusside (0.2 μg/g) was injected into the pulmonary artery, and the resultant changes in vascular pressure were recorded. Across all age groups, with and without DA1 receptor blockade, sodium nitroprusside–induced vasodilation was similar (–2.7 ± 0.2 mm Hg) and was considered reference vasodilation. The fenoldopam vasodilation response was considered a percentage of the sodium nitroprusside reference. Response to fenoldopam varied significantly (p < 0.05 by analysis of variance) across the six age groups, with a maximum at 3–5 d of age. Pretreatment with SCH 23390, a selective DA1-blocking agent, significantly attenuated fenoldopam vasodilation in all but the youngest animals (age 0–2 d), in which no blockade effect was noted. We conclude that there are significant age-related changes in the vascular responses to fenoldopam. We speculate that endogenous dopamine and vascular dopamine receptors may play a role in mediating changes in the transitional, pulmonary circulation.

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